PB1863: VENETOCLAX AND HYPOMETHYLATING AGENT BASED OUTPATIENT AML INDUCTION- COST-EFFECTIVE METHOD FOR LMICS-REAL WORLD DATA FROM A TERTIARY CARE CENTER
Authors: Priyanka Chauhan, Nihar Desai, Shilpi Agarwal, Archit Pandharipande, Sanjeev Yadav, Anshul Gupta, Manish Kumar Singh, Dinesh Chandra, Khaliqur Rehman, Ruchi Gupta, Rajesh Kashyap, Soniya Nityanand
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: Venetoclax in combination with azacytidine, decitabine or low dose ARA-C has been approved as an upfront therapy for elderly patients (75 years or above) of AML or those who are ineligible for intensive induction therapy based on the results of Viale A and Viale C phase 3 trials. However, the criteria of ineligibility for intensive induction in LMICs is not just age. Many younger patients could not be given intensive induction due to baseline serious infections, financial issues and/or lack of social support. Aims: To study the efficacy and cost effectiveness of Venetoclax and Hypomethylating agent-based induction in newly diagnosed and relapsed refractory Acute myeloid leukemia. Methods: This retrospective single centre study was conducted at a tertiary care institute in India between 2020 and 2022 where 57 patients of newly diagnosed (Age>60 years, Baseline non-resolving infection, lack of financial resources, diagnosed during second covid wave) or relapsed refractory AML received off label VEN-HMA based induction therapy. The results were compared with 27 patients receiving Intensive Induction therapy (ARM B) at our centre during the same period. Informed consent was taken from all patients <75 years for off label use of VEN-HMA. The cut-off date for last follow up was September 2022 Results: Between April 2020 and June 2022, 57 patients, median age 48 years (Range 11-78), of Acute myeloid leukemia (35 newly diagnosed and 22 relapsed refractory) were treated with Venetoclax and Hypomethylating agents (Azacytidine/Decitabine). The Overall complete response rate (ORR) was 72.7% with Complete Remission (CR), Complete Remission with incomplete count recovery (CRi) rates of 57.9% and 15.8% respectively, was statistically comparable to ORR of patients receiving intensive induction 62.96% (p value-0.251). The median number of cycles of VEN-HMA for CR/CRi was 1(1-3). Median overall survival (OS) in VEN-HMA patients was 19 months which was statistically superior to OS of 13±2.78 months in ARM B (log rank test-0.025) while Median progression free survival (PFS) was superior in ARM B (17months vs 14 months in VEN- HMA arm, p-value-0.020). Median OS and PFS were significantly superior in newly diagnosed (OS-19 months, pvalue-0.044, PFS-14±1.1 months, p value-0.011) when compared with relapsed/refractory patients(OS-12±2.2 months, PFS-9±1.7 months). Median time from diagnosis to treatment was significantly lower (p value-0.016),13 days (0-29) in VEN-HMA arm vs 35(3-165) days in ARM B. Grade 3-4 adverse events were lower in VEN-HMA arm. 48(84.21) vs 27(100%) in ARM B. Induction deaths in VEN-HMA arm was 8/57(14%) while in ARM B it was 8/27 (30%). Duration of hospital stay in VEN-HMA in cycle 1 was 7 days (1-22) compared to 27 days (14-68) in ARM B (p value <0.001) and cost of therapy in VEN-HMA arm ($1429.9±132.5) was significantly lower than in ARM B ($3927.2±823.9) (p value<0.001) In this study patients who received consolidation with Allogenic stem cell transplant(N=5) or high dose cytarabine(N=6) post attainment of CR with VEN-HMA had superior OS (Mean OS-18.40±0.80 vs 12.97±1.0 months, p-value-0.029) and PFS(Mean 16.60±0.82 vs 10.44±1.0 months, p-value-0.034) as compared to those who were continued on VEN-HMA. Summary/Conclusion: Venetoclax and hypomethylating agent outpatient-based induction for AML is a feasible approach in both newly diagnosed and relapsed refractory cases especially in LMICs due to lower cost, less duration of hospital stay, less delay in therapy, decreased transfusion requirement. However, research should focus on appropriate consolidation strategy in fit patients who achieve CR post VEN-HMA.Keywords: Acute myeloid leukemia